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For the first time, a polyclonal antibody with high affinity to atorvastatin (ATR) was generated. The high specificity of the antibody for ATR among its structural analogues and co-administered therapeutic agents was proved. The antibody was employed in the development of enzyme-linked immunosorbent assay for quantitation of ATR in plasma. The assay was validated over a working range of 0.2-5 ng/mL. The intra- and interassay precisions were satisfactory; the coefficients of variations were ≤5%. The accuracy of the method was proved as the mean recovery was 96.4 ± 4.3%. The assay can be used in therapeutic monitoring and pharmacokinetic studies for ATR. [ABSTRACT FROM AUTHOR]

This study describes the development and validation of a highly sensitive and specific enzyme immunoassay (EIA) for therapeutic monitoring and pharmacokinetic studies of atorvastatin (ATR). The assay employs a polyclonal antibody that recognizes ATR with high specificity and affinity, and ATR conjugated to bovine serum albumin (ATR-BSA) immobilized onto microwell plates as a solid phase. The assay involved a competitive binding reaction between ATR and the immobilized ATR-BSA for the binding sites on a limiting amount of the anti-ATR antibody. The bound anti-ATR antibody was quantified with horseradish peroxidase-labeled anti-immunoglobulin secondary antibody and 3,3′,5,5′-tetramethylbenzidine as a substrate for the peroxidase enzyme. The concentration of ATR in the sample was quantified by its ability to inhibit the binding of the anti-ATR antibody to the immobilized ATR-BSA and subsequent color development in the assay wells. The conditions for the EIA were investigated and optimized for the determination of ATR in plasma samples. The limit of detection was 0.04 ng mL−1 and the effective working range at relative standard deviations (RSD) of ≤5% was 0.1–10 ng mL−1. Mean analytical recovery of ATR from spiked plasma was 99.3 ± 2.8%. The precision of the assay was satisfactory; RSD were 2.7–4.6 and 3.3–5.7% for intra- and inter-assay precision, respectively. The reliability of the EIA was confirmed by HPLC. The EIA is convenient, and one can analyze ∼ 200 samples per working day, facilitating the processing of large-number of samples of ATR. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Imaging tumor response to neoadjuvant chemotherapy in vivo offers unique opportunities for patient care and clinical decision-making. Detailed imaging studies may allow oncologists to optimize therapeutic drug type and dose based on individual patient response. Most radiologic methods are used sparingly because of cost; thus, important functional information about tumor response dynamics may be missed. In addition, current clinical standards are based on determining tumor size changes; thus, standard anatomic imaging may be insensitive to early or frequent biochemical responses. Because optical methods provide functional imaging end points, our objective is to develop a low-barrier-to-access bedside approach that can be used for frequent, functional assessment of dynamic tumor physiology in individual patients. Materials and Methods: Diffuse Optical Spectroscopic Imaging (DOSI) is a noninvasive, bedside functional imaging technique that quantifies the concentration and molecular state of tissue hemoglobin, water, and lipid. Pilot clinical studies have shown that DOSI may be a useful tool for quantifying neoadjuvant chemotherapy response, typically by comparing the degree of change in tumor water and deoxy-hemoglobin concentration before and after therapy. Patient responses at 1 week and mid-therapy have been used to predict clinical outcome. In this report, we assess the potential value of frequent DOSI monitoring by performing measurements on 19 different days in a 51-year-old subject with infiltrating ductal carcinoma (initial tumor size 60 × 27 mm) who received neoadjuvant chemotherapy (anthracyclines and bevacizumab) over an 18-week period. Results: A composite index, the Tissue Optical Index (TOI), showed a significant (∼50%) decrease over the nearly 18 weeks of chemotherapy. Tumor response was sensitive to the type of chemotherapy agent, and functional indices fluctuated in a manner consistent with dynamic tumor physiology. Final pathology revealed 4 mm of residual disease, which was detectible by DOSI at the conclusion of chemotherapy before surgery. Conclusion: This case study suggests that DOSI may be a bedside-capable tool for frequent longitudinal monitoring of therapeutic functional response to neoadjuvant chemotherapy. [Copyright &y& Elsevier]

Abstract: Purpose: To assess early radiation therapy (RT)-induced variations in total choline (tCho) concentration measured by proton magnetic resonance spectroscopy (H-MRS) and in 18F-labelled fluoromethylcholine (FCH) uptake measured by PET in a rodent tumour model. Methods: Nine rats bearing syngenic rhabdomyosarcoma grafts in both thighs were irradiated (13 Gy, one fraction). H-MRS data and FCH-PET were acquired in the same imaging session prior to and 3, 9 and 16 days after external RT. Total choline concentration was expressed in arbitrary units as the area under the curve of the 3.2-ppm peak on H-MR spectra. FCH uptake was expressed as maximum standardized uptake value (SUVmax) and as the % of injected dose per gram (%ID/g) after precise tumour delineation on hybrid PET-MR images. Pre- and post-RT data were compared using the Student''s paired t test, and results were expressed as mean±S.D. Results: Seventeen tumours were available for analysis. A mean drop in choline concentration of 45% was observed 3 days after irradiation (P<.001), whereas a concomitant mean increase in SUVmax of 41% was observed (P=.006). Choline concentration reincreased on later time points. Conclusions: Opposite trend between increased FCH uptake and decreased tCho peak was observed at 3 days. Later (9 and 16 days), uptake remained stable and tCho peak reincreased. [Copyright &y& Elsevier]

The management of heart failure remains challenging despite many therapeutic advances. Rigorous clinical trial evidence supports administration of multiple therapies, but utilization of evidence-based treatment remains inconsistent and suboptimal. Disease management programs appear effective, but remain costly and difficult to implement in today's care system. Another approach involves optimizing therapy based on serial monitoring of cardiac biomarkers. Emerging results suggest that guiding therapy based on serial changes in natriuretic peptides may be an effective strategy. Although pilot work has provided encouraging results, appropriately designed, large-scale, prospective randomized trials are needed to confirm these preliminary findings and definitively establish this therapeutic approach. [ABSTRACT FROM AUTHOR]

In 2009, the US Food and Drug Administration approved three medications for the treatment of epilepsy: rufinamide, lacosamide, and vigabatrin. In addition, extended-release formulations of lamotrigine and levetiracetam were approved recently. When added to the dozen medications for treating epilepsy, the choice is a luxury in terms of additional options, but also a challenge for practitioners to use them all with expertise. Recently, there has been much interest surrounding medications for epilepsy and their possible association with osteoporosis, safety during pregnancy, biological equivalence to generic versions, and possible association with higher rates of suicidality. This review discusses these issues and provides a current overview for the medical management of epilepsy. [ABSTRACT FROM AUTHOR]

Owing to the excellent barrier properties of the stratum corneum, transdermal delivery remains a challenge for a high number of molecules. Iontophoresis is a noninvasive technique which uses a low current to administer polar and charged species through the skin, thereby enlarging the range of drug candidates for transdermal administration. Unlike other techniques of transdermal delivery enhancement, iontophoresis acts on the molecule itself allowing a better control of the dose applied. The symmetry of the technique can be employed for controlled extraction, allowing a relation to be established between extracted flux and subdermal concentration. This opened the way for innovative applications, notably in the field of noninvasive monitoring of glucose and xenobiotics. Rather than being an extensive review of the literature, this article summarizes the basic rules governing iontophoretic transport, discusses advantages and limitations of the technique, and provides an overview of promising therapeutic applications. [ABSTRACT FROM AUTHOR]

Copyright of Bio Tribune Magazine is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Introduction: The impact of the TB-info® software was assessed on the care of patients treated with antituberculosis regimen (ATT). Methods: Cohort study of patients with tuberculosis who received an ATT in 2004 in two hospitals and five medical centres in Paris. Follow-up was implemented with the TB-Info® software. Data were compared to those of the 1999–2003 cohort. Results: Two hundred and nine ATT were initiated in 2004, with a mean duration of 7.2 months. Demographic and clinical data reflected this population precariousness: 79% were foreign-born, 25% lived in institutions and half of them had no or unusual health insurance. Compared to the previous cohort, viral co-infections were tested in more than 80% cases and showed association with HIV, HBV or HCV in 11, 10 and 5% of the patients, respectively. Twenty-one patients were lost for follow-up (11%) and 76% of the smear-positive pulmonary tuberculosis therapies were declared successful but only 34% were declared cured with the WHO criteria. Conclusion: Analysis of the data obtained with TB-info® software showed an improvement of tuberculosis patients care with more co-infection tested and less lost for follow-up. These results confirm the usefulness of this software for patients care and assessment of physicians practice in France. [Copyright &y& Elsevier]

Abstract: Purpose: The goals of this study are to evaluate the efficacy and tolerability of levetiracetam (LEV) as add-on therapy in children with refractory epilepsies and to determine the value of LEV blood level monitoring in this population. Methods: Sixty-nine children (39 males and 30 females) treated with LEV between 2006 and 2007 were selected. Their medical files were reviewed for LEV efficacy and tolerability. In a subgroup of children currently taking LEV, plasma concentrations were determined by high performance liquid chromatography by ultraviolet detection (HPLC-UV) method and correlated with the given dose per kilo as well as clinical response. Results: Fifty-one patients (74%) had a more than 50% reduction in seizure frequency with 16 patients (23%) becoming seizure free on LEV. Eighteen (26%) patients had a less than 50% reduction in seizure frequency. Adverse events due to LEV ranged from mild to moderate in only 18 patients (26%). The most frequently observed were drowsiness, behavioral difficulties, increase in seizure frequency and headaches. The majority (60.5%) of the responders received doses between 10 and 50mg/kg/day and had a plasma concentration (PC) between 5 and 40μg/ml. However, we found no clear correlation between PC and efficacy. Conclusion: Levetiracetam given twice a day in children with refractory epilepsy reduces seizure frequency in all types of epilepsy. In children, LEV is a broad spectrum anticonvulsant with a favourable safety profile. [Copyright &y& Elsevier]

Abstract: Reverse iontophoresis across the skin is a potentially useful alternative for non-invasive clinical and therapeutic drug monitoring. In this work, the reverse iontophoretic extraction of 17 amino acids was studied in vivo in healthy volunteers. Charged amino acids were primarily extracted towards the electrode of opposite polarity, while zwitterionic species were extracted, more or less equally, to both anode and cathode, suggesting that the net charge on the skin, under the conditions of the experiment, was close to zero. The significant presence of a ‘skin reservoir’ of several amino acids, presumably originating from the barrier’s so-called ‘natural moisturising factor’, was deduced from the results. While this phenomenon had been observed in an earlier in vitro investigation, the levels of certain amino acids (including serine and glycine) in the skin were found to be much higher in vivo. Hence, while the results of this study confirm the feasibility of extracting some amino acids at physiologically relevant levels in vivo, the objective of achieving a correlation between iontophoretically extracted fluxes and blood plasma levels may not be a practically realisable goal in all cases. [Copyright &y& Elsevier]

Abstract: Reverse iontophoresis across the skin has been investigated as alternative, non-invasive method for clinical and therapeutic drug monitoring. This research investigated the reverse iontophoretic extraction of 19 amino acids present at clinically relevant levels in the subdermal compartment of an in vitro diffusion cell. Over a simulated, systemic concentration range of 0–500μM, the extraction of amino acids was linear. Charged amino acids were extracted towards the electrode of opposite polarity, while zwitterionic species were extracted to both anode and cathode with the latter predominating. The reverse iontophoretic extraction flux was a linear function of amino acid isoelectric point, reflecting the different contributions of electromigration and electroosmosis to electrotransport. Overall, the results confirm the feasibility of monitoring amino acids at clinically relevant levels and provide an incentive for in vivo research to further explore the clinical potential of reverse iontophoresis for the non-invasive monitoring of amino acids. [Copyright &y& Elsevier]

Nucleosomes, complexes of DNA and histone proteins, are released during cell death into the blood circulation. Elevated serum and plasma levels have been found in various forms of cancer, but also in autoimmune diseases and acute situations such as stroke, trauma, and during sepsis. Here, the clinical relevance of circulating nucleosomes for diagnosis, staging, prognosis, and therapeutic monitoring of cancer is reviewed. Several studies have shown that levels of nucleosomes are significantly higher in serum and plasma of cancer patients in comparison to healthy controls. However, because of elevations of nucleosome levels in patients with benign diseases relevant for differential diagnosis, they are not suitable for cancer diagnosis. Concerning tumor staging, nucleosome levels correlate with tumor stage and presence of metastases in gastrointestinal cancer, but not in other tumor types. Prognostic value of circulating nucleosomes is found in lung cancer in univariate analyses, but not in multivariate analyses. Circulating nucleosomes are most informative for the monitoring of cytotoxic therapy. Strongly decreasing levels are mainly found in patients with remission of disease, whereas constantly high or increasing values are associated with progressive disease during chemo- and radiotherapy. In addition, therapy outcome is already indicated by the nucleosomal course during the first week of chemo- and radiotherapy in patients with lung, pancreatic, and colorectal cancer as well as in hematologic malignancies. Despite their non-tumor-specificity, kinetics of nucleosomes are valuable markers for the early estimation of therapeutic efficacy and may be helpful to adapting early cancer therapy in the future. [ABSTRACT FROM AUTHOR]

Summary: Objective: The anemic status may alter brain functions and electrogenesis, as reflected by EEG and cognitive EPs (CEPs). This study aims to evaluate CEPs and EEG power spectra in adult patients with iron-deficiency anemia and to determine the effects of appropriate iron therapy on electrodiagnostic findings. Methods: Fifty-one patients with iron-deficiency anemia underwent CEP and EEG recording. All patients were re-assessed after three months of oral-iron therapy. Results: All patients had recovered from their anemia through the three-month iron therapy. Central N1 amplitude and parietal P2 amplitude was increased. N2 latencies were shortened in frontal and central regions. P3 latencies were shortened in frontal, central and parietal areas and P3 amplitude was increased in the parietal region. Except in the gamma-band, all pretreatment and post-treatment mean-power values were significantly lower at the temporal, parietal and occipital regions. Conclusions: This study indicates that in iron-deficiency anemia, appropriate iron therapy can improve brain electrogenesis, as reflected by P300 and EEG power spectra. [Copyright &y& Elsevier]

Abstract: We developed a novel diagnostic system for continuous peritoneal dialysis, which evaluates the peritoneal permeability and hydraulic conductance (peritoneal function) by applying the kinetic model and a clinical test with minimum nursing time. Kinetic parameters for the peritoneal function were determined by the simultaneous numerical optimization techniques (SNOT). Furthermore dialysis outcome and ultrafiltration volume were estimated and predicted by using the kinetic model with a set of optimal kinetic parameters, which were in agreement with measured data . The clinical implementation of the SNOT is very useful to explore the better prescriptions for each patient''s clinical condition. [Copyright &y& Elsevier]

Analysis of exhaled breath condensate (EBC) is a noninvasive method for studying the composition of airway lining fluid and has the potential for assessing lung inflammation. EBC is mainly formed by water vapor, but also contains aerosol particles in which several biomolecules including leukotrienes, 8-isoprostane, prostaglandins, hydrogen peroxide, nitric oxide-derived products, and hydrogen ions, have been detected in healthy subjects. Inflammatory mediators in EBC are detected in healthy subjects and some of them are elevated in patients with different lung diseases. Analysis of EBC is completely noninvasive, is particularly suitable for longitudinal studies, and is potentially useful for assessing the response to pharmacological therapy. Identification of selective profiles of biomarkers of lung diseases might also have a diagnostic value. However, EBC analysis currently has important limitations. The lack of standardized procedures for EBC analysis and validation of some analytical techniques makes it difficult comparison of results from different laboratories. Analysis of EBC is currently more useful for relative measures than for quantitative assessment of inflammatory mediators. Reference analytical techniques are required to provide definitive evidence for the presence of some inflammatory mediators in EBC and for their accurate quantitative assessment in this biological fluid. Several methodological issues need to be addressed before EBC analysis can be considered for clinical applications. However, further research in this area is warranted due to the relative lack of noninvasive methods for assessing lung inflammation. [ABSTRACT FROM PUBLISHER]

A pharmacokinetic–pharmacodynamic study was carried out to investigate the feasibility and potential importance of therapeutic monitoring following high-dose carboplatin treatment in children. High-dose carboplatin was administered over 3 or 5 days, with the initial dose based on renal function, to achieve target area under the plasma concentration–time curve (AUC) values of 21 or 20 mg ml−1.min, respectively. Dose adjustment was carried out based on observed individual daily AUC values, to obtain the defined target exposures. Platinum–DNA adduct levels were determined in peripheral blood leucocytes and toxicity data were obtained. Twenty-eight children were studied. Based on observed AUC values, carboplatin dose adjustment was performed in 75% (21 out of 28) patients. Therapeutic monitoring resulted in the achievement of carboplatin exposures within 80–126% of target AUC values, as compared to estimated exposures of 65–213% of target values without dose adjustment. The carboplatin AUC predicted with no dose modification was positively correlated with pretreatment glomerular filtration rate (GFR) values. Higher GFR values were observed in those patients who would have experienced AUC values >25% above the target AUC than those patients attaining AUC values >25% below the target AUC, following renal function-based dosing. Platinum–DNA adduct levels correlated with observed AUC values on day 1 of carboplatin and increased over a 5-day course of treatment. Real-time monitoring of carboplatin pharmacokinetics with adaptive dosing is both feasible and necessary for the attainment of consistent AUC values in children receiving high-dose carboplatin treatment. Pharmacodynamic data suggest a strong correlation between carboplatin pharmacokinetics and the drug–target interaction.British Journal of Cancer (2007) 96, 725–731. doi:10.1038/sj.bjc.6603607 www.bjcancer.com Published online 13 February 2007 [ABSTRACT FROM AUTHOR]

Invasive aspergillosis is a serious and lethal infection among immunocompromised patients, with reported mortality rates as high as 74-92%. The high mortality is related to the severe immunosuppression experienced by these patients as well as the difficulties for physicians in arriving at a timely diagnosis. Definitive diagnostic procedures (tissue biopsy for histopathology and culture) are often precluded by severe cytopenias and coagulation abnormalities. The development of minimally invasive, nonculture diagnostic methods is a major advance in the early diagnosis of invasive aspergillosis. Galactomannan is a heteropolysaccharide (mannan core and side residues of galactofuranosyl units) present in the cell wall of Aspergillus spp. The double sandwich enzyme immunoassay, which detects galactomannan in serum samples, has been available in Europe for almost a decade and in the USA since May 2003, for the diagnosis of invasive aspergillosis. However, availability of the double galactomannan enzyme immunoassay is center variable in the USA and, although its analytical performance in the diagnosis of invasive aspergillosis is well documented, its routine use in clinical practice is limited. As an adjunct in the diagnosis and management of invasive aspergillosis, incorporation of the galactomannan enzyme immunoassay into clinical trials will help to further define its role. [ABSTRACT FROM AUTHOR]

Abstract: A sensitive high-performance liquid chromatographic (HPLC) method was developed for warfarin determination in plasma of patients who undertook cardiac valve replacement and were on anticoagulation with warfarin. The method described proved to be accurate, sensitive, easy to perform, reproducible and specific for plasma warfarin measurement with relative standard deviation (R.S.D.) of <5.27% for inter-day and <6.89% for intra-day. The assay was linear in warfarin concentration ranges of 0.12–3μg/ml (r =0.9995) with mean recovery of 94.6%. The mean warfarin plasma concentration of 58 patients with heart valve replacement within 1 month of post operation was 567.6±122.3ng/ml. The anticoagulant effect of the drug was monitored by international normalized ratio (INR). The correlation of warfarin dosage and concentration with INR was analysed, and the coefficients were 0.21, 0.1

Purpose: The role of FDG-PET in primary central nervous system lymphoma (PCNSL) is unclear. It was the aim of this study to investigate the role of FDGPET in detecting PCNSL and in predicting response to chemotherapy. Methods: An FDG-PET scan of the brain was performed in 15 patients with histologically proven PCNSL (16 PET examinations, Siemens ECAT EXACT). PET was planned to investigate patients at the time of primary diagnosis, after chemotherapy and at the time of suspected relapse in seven, five and three cases, respectively. All except two patients simultaneously underwent MRI of the brain. FDG-PET results were correlated with histological results after stereotactic biopsy (primary diagnosis group) and with clinical data and MRI during follow-up. Results: Six of the seven patients in the primary diagnosis group demonstrated a true positive finding (86%). In one of the true positive PET patients, there were two tumour lesions, one of which was only detectable on the FLAIR MRI sequence. In five patients, FDG-PET showed no sign of PCNSL during ongoing chemotherapy. These results were confirmed by the clinical follow-up (mean 26.6 months). MRI demonstrated minimal residual disease which had disappeared on further follow-up MRI in three of these five patients at the time of PET scanning. Recurrence of disease was confirmed concordantly by FDGPET and MRI in three different patients. The standardised uptake value of all tumours was 10.2 (4.3-13.7). Conclusion: PCNSLs demonstrate high FDG uptake and can be diagnosed by FDG-PET with high sensitivity. It seems that FDG-PET is suitable for early therapeutic monitoring after chemotherapy. [ABSTRACT FROM AUTHOR]

We present noninvasive, quantitative in vivo measurements of methemoglobin formation and reduction in a rabbit model using broadband diffuse optical spectroscopy (DOS). Broadband DOS combines multifrequency frequency-domain photon migration (FDPM) with time-independent near infrared (NIR) spectroscopy to quantitatively measure bulk tissue absorption and scattering spectra between 600 nm and 1,000 nm. Tissue concentrations (denoted by brackets) of methemoglobin ([MetHb]), deoxyhemoglobin ([Hb-R]), and oxyhemoglobin ([HbO2]) were determined from absorption spectra acquired in ‘real time’ during nitrite infusions in nine pathogen-free New Zealand White rabbits. As little as 30 nM [MetHb] changes were detected for levels of [MetHb] that ranged from 0.80 to 5.72 μM, representing 2.2 to 14.9% of the total hemoglobin content (%MetHb). These values agreed well with on-site ex vivo cooximetry data (r² = 0.902, P < 0.0001, n = 4). The reduction of MetHb to functional hemoglobins was also carried out with intravenous injections of methylene blue (MB). As little as 10 rim changes in [MB] were detectable at levels of up to 150 nM in tissue. Our results demonstrate, for the first time, the ability of broadband DOS to noninvasively quantify real-time changes in [MetHb] and four additional chromophore concentrations ([Hb-R], [HbO2], [H2O], and [MB]) despite significant overlapping spectral features. These techniques are expected to be useful in evaluating dynamics of drug delivery and therapeutic efficacy in blood chemistry, human, and preclinical animal models. [ABSTRACT FROM AUTHOR]

Circulating tumours cells (CTCs) represent an important biologic link in the spread of breast cancer from primary to metastatic disease. CTCs are strong predictors of prognosis in patients with metastatic breast cancer. Research to date has focused on development of methods with adequate sensitivity and specificity to reproducibly identify these rare events. Future research will focus on the biologic phenotypes of these cells with goals to understand mechanisms of metastasis, to identify novel therapeutic targets, and to monitor response to therapy. [ABSTRACT FROM AUTHOR]

Abstract: A biosensor is a sensor that uses biological selectivity to limit its perception to particular key molecules and can be defined as an analytical device possessing a biological or biologically derived sensing element integrated with or associated closely with a physicochemical transducer. In the future it is likely that a number of key developments in therapeutic monitoring and intelligent drug delivery will rely on real-time feedback information in order to deliver an appropriate response. However due to issues of integration and the fragility and unreliability of the bio-molecule, biosensors are currently unable to fulfil this role. Molecular imprinted polymers are viable alternatives to both antibodies and enzymes and this review considers the current position of molecular imprinted polymer sensing. [Copyright &y& Elsevier]

Abstract: The authors developed a computer-aided diagnosis system that includes a simple clinical test for the chronic renal disease patient who needs an integrated approach that combines both peritoneal dialysis and hemodialysis (PD–HD therapy). In this case study, the system simulated and estimated the dialysis outcome, the ultrafiltration volume and nutritional analysis by employing a pharmacokinetic model, and assessed the peritoneal permeable enhancement that can be a grave complication with peritoneal dialysis. This system requires only a minimum amount of nursing time and may be able to predict the optimal treatment schedule for PD–HD therapy and provide therapeutic monitoring in long-term peritoneal dialysis. [Copyright &y& Elsevier]

Abstract: Quantitation of circulating hepatitis B virus (HBV) DNA is important for monitoring disease progression and for assessing the response to antiviral therapy. Several commercial and ‘in house’ assays for HBV DNA quantitation have been described but many of these have limitations of relatively low sensitivity and limited dynamic range. This study describes the development and evaluation of a FRET-based real-time PCR assay designed to overcome these limitations and to provide accurate quantitation of DNA from all eight genotypes of HBV (A–H). The assay employs a fully automated nucleic acid extraction system permitting high-sample throughput with minimal ‘hands-on’ time and incorporates a murine cytomegalovirus (mCMV) internal control to prevent false negative results and under-reporting due to unrecognised problems with viral lysis, DNA purification or PCR amplification. Sensitivity, assessed by Probit analysis at the 95% detection level, was 24.4IU/ml, associated with an extremely wide dynamic range (∼9log10). Coefficients of variation were low for both intra-assay and inter-assay variability (CV%, 7–11%) and quantitative data correlated well (R 2 =0.97) with the Digene hybrid capture assay. This assay provides an ideal system for therapeutic monitoring and for studying the relationship between HBV viral load and stage of disease. [Copyright &y& Elsevier]

Copyright of Revue Francaise des Laboratoires is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To determine the ability of community pharmacists within an anticoagulation clinic to keep international normalized ratios (INRs) within therapeutic ranges and, secondarily, to determine the incidence of bleeding and thromboembolic events and patient satisfaction.Design: Retrospective observational study.Setting: Eckerd PatientCARE Network in Eckerd pharmacies in Tampa Bay area of Florida.Patients: 50 patients taking warfarin and having INR determinations for 6 consecutive months.Interventions: Clinical pharmacists monitored patients' anticoagulation status using point-of-care analyzers and making dosage changes as needed under a collaborative agreement. Extensive patient education was provided to patients regarding their anticoagulation. Data were collected from the initial visit through the 6 consecutive months. Patients were surveyed to assess their satisfaction with the clinic.Main Outcome Measures: Percentage of INRs within therapeutic range and, secondarily, incidence of bleeding and thromboembolic events and patient satisfaction with the clinic.Results: During the 6 months of initial therapy with warfarin, 243 of 435 (56%) INRs were in desired therapeutic ranges. A total of 15 bleeding episodes were reported, of which 10 were minor and 5 were significant. No thromboembolic events were reported. There was a 22% response rate to the survey, in which all statements were rated as above average to excellent.Conclusion: Community pharmacists in an anticoagulation clinic effectively manage anticoagulation therapy, as the results of this clinic are similar to those of clinics managed by pharmacists in other settings. [ABSTRACT FROM AUTHOR]